Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen.
The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled.
NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 11 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.
NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 11 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.High resolution manometry (HRM), developed from conventional manometry, is the gold standard for assessment of esophageal motor function worldwide. The Chicago Classification, now in its fourth iteration, is the modern standard for HRM categorization of esophageal motility disorders. The HRM protocol has expanded from the original 10 supine swallow standard, to include upright swallows, and provocative maneuvers such as multiple rapid swallows, rapid drink challenge and standardized test meal. Impedance has been incorporated into HRM for visualization of bolus clearance. Futhermore, barium radiography and functional lumen imaging probe complement HRM when evidence of esophagogastric junction obstruction is inconclusive. The biggest impact of HRM is in the improved diagnosis and subtyping of achalasia spectrum disorders, with implications on management. Spastic disorders and absent contractility are better characterized. Within the reflux spectrum, HRM provides definition of morphology and tone of the esophagogastric junction, and assesses integrity of esophageal body peristalsis, which have pathophysiologic implications for reflux and its clearance. HRM provides characterization of behavioral disorders such as supragastric belching and rumination syndrome, which can mimic reflux disease. Thus, HRM has revolutionized the evaluation of esophageal motor function, and has expanded the utility of esophageal manometry in clinical practice.Mutations arising early in human development are surprisingly common, but most often are confined to the placenta. These mutations provide clues to the normal developmental processes leading to a healthy placenta, despite these features being shared in common with cancer.Pemphigus vegetans is a rare variant of pemphigus vulgaris. Here, we report a rare case of postparturition pemphigus vegetans in a young woman without any prior medical history. The patient presented with extensive oral mucosal erosion, conjunctivitis, and fingernail dystrophy. A histopathological biopsy taken from the tongue showed pseudoepitheliomatous hyperplasia of the epidermis with eosinophilic spongiosis, and an intraepidermal cleft and direct immunofluorescence showed intercellular immunoglobulin G and complement component C3 deposition. A final diagnosis of pemphigus vegetans was made on the basis of clinical and histopathological features and laboratory findings. Complete remission was achieved by a combination of methylprednisolone and thalidomide. This case report indicates that the occurrence of postparturition pemphigus vegetans is strongly associated with immune status related to hormone levels throughout pregnancy and postparturition. Furthermore, it suggests that a combination of methylprednisolone and thalidomide may be an effective option for pemphigus vegetans treatment.Neurodevelopmental disorders (NDDs) are a set of complex disorders characterized by diverse and co-occurring clinical symptoms. https://www.selleckchem.com/products/eflornithine-hydrochloride-hydrate.html The genetic contribution in patients with NDDs remains largely unknown. Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations (DNMs) in 86 genes and 2,385 rare inherited mutations (RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of 16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes - ITSN1, UBR3, CADM1, RYR3, FLNA, and PLXNA3 - preferably contribute to autism spectrum disorders (ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs, further facilitating both basic and translational research.